Sex Chromosome Constitution Research Articles

The establishment of sexual identity in the Drosophila germline.

The establishment of sexual identity is a crucial step of germ cell development in sexually reproducing organisms. Sex determination in the germline is controlled differently than in the soma, and often depends on communication from the soma. To investigate how sexual identity is established in the Drosophila germline, we first conducted a molecular screen for genes expressed in a sex-specific manner in embryonic germ cells. Sex-specific expression of these genes is initiated at the time of gonad formation (stage 15), indicating that sexual identity in the germline is established by this time. Experiments where the sex of the soma was altered relative to that of the germline (by manipulating transformer) reveal a dominant role for the soma in regulating initial germline sexual identity. Germ cells largely take on the sex of the surrounding soma, although the sex chromosome constitution of the germ cells still plays some role at this time. The male soma signals to the germline through the JAK/STAT pathway, while the nature of the signal from the female soma remains unknown. We also find that the genes ovo and ovarian tumor (otu) are expressed in a female-specific manner in embryonic germ cells, consistent with their role in promoting female germline identity. However, removing the function of ovo and otu, or reducing germline function of Sex lethal, had little effect on establishment of germline sexual identity. This is consistent with our findings that signals from the soma are dominant over germline autonomous cues at the initial stage of germline sex determination.

Two cases of sex chromosome aberration XXXXY

HereditasVolume 55, Issue 1 p. 126-128 Open Access Two cases of sex chromosome aberration XXXXY Sindey Aronsson, Sindey Aronsson Clinic of Pediatrics, University Hospital, and Institute of Genetics, Lund, SwedenSearch for more papers by this authorFredrik Lindgren, Fredrik Lindgren Clinic of Pediatrics, University Hospital, and Institute of Genetics, Lund, SwedenSearch for more papers by this authorLeif Svanström, Leif Svanström Clinic of Pediatrics, University Hospital, and Institute of Genetics, Lund, SwedenSearch for more papers by this author Sindey Aronsson, Sindey Aronsson Clinic of Pediatrics, University Hospital, and Institute of Genetics, Lund, SwedenSearch for more papers by this authorFredrik Lindgren, Fredrik Lindgren Clinic of Pediatrics, University Hospital, and Institute of Genetics, Lund, SwedenSearch for more papers by this authorLeif Svanström, Leif Svanström Clinic of Pediatrics, University Hospital, and Institute of Genetics, Lund, SwedenSearch for more papers by this author First published: August 1966 https://doi.org/10.1111/j.1601-5223.1966.tb02041.xAboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Literature cited Day, R. W., Levinson, J., Larson, W. and Wright, S. W. 1963. An XXXXY male. J. Pediat. 63: 589– 598. Denver, Human Chromosomes Study Group. 1960. A proposed standard of nomenclature of human mitotic chromosomes. Cerebral Palsy Bull. 2, Suppl., 9 p. Kaijser, K. 1964. Könskromosomaberrationen XXXXY (The abnormal sex-chromosome constitution XXXXY). Nord. Med. 71: 105– 108. Moorhead, P. S., Nowell, P. C., Mellman, W. J., Battips, D. M. and Hungerford, D. A. 1960. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp. Cell Res. 20: 613– 616. Volume55, Issue1August 1966Pages 126-128 ReferencesRelatedInformation

Review and Update: Genomic and Molecular Advances in Sex Determination and Differentiation in Small Animals

Inherited disorders of sexual development are important to identify as a cause of inherited infertility or sterility in humans and animals. Investigation of these disorders in dogs and cats can identify new mutations, allowing us to eliminate inherited disorders from breeding populations, while contributing to the understanding of mammalian sexual development and differentiation. This review updates an overview of normal mammalian sexual development while discussing disorders of sexual development at three consecutive levels, as errors in sex chromosome constitution, gonadal sex determination or phenotypic sexual development. The molecular mechanisms controlling sexual development and current molecular methods to identify causative mutations are illustrated in three specific examples of abnormal sexual development reported in small animals: XX sex reversal, Persistent Mullerian Duct Syndrome and cryptorchidism. Identification of causative mutations and development of practical tests to identify carrier and affected animals will provide effective mechanisms to reduce the prevalence of these disorders in small animals.

Focal spermatogenesis originates in euploid germ cells in classical Klinefelter patients

Klinefelter syndrome is the most frequent chromosome abnormality in human males. This paper aims to investigate the ploidy of meiotic and pre-meiotic germ cells found in spermatogenic foci, and furthermore, the sex chromosome constitution of Sertoli cells which surround these germ cells in non-mosaic Klinefelter patients. A survey of 11 adult patients diagnosed with classical, non-mosaic Klinefelter syndrome who underwent testicular biopsies, showed that six of them had spermatogenesis foci. The topographical study of the biopsies showed that tubuli with germ cells are a minor fraction (8-24%) of all tubuli, although the overwhelming majority is devoid of germ cells. Using fluorescence in situ hybridization (FISH) with probes for the X-centromere and immunolocalization of meiotic proteins, the present work shows that all the 92 meiotic spermatocytes analyzed with FISH were euploid, 46,XY, and thus can form normal, haploid gametes. On the other hand, Sertoli cells show two marks for the X chromosome, meaning that they are 47,XXY. These results provide a rationale for the high rate of success in the testicular sperm extraction plus ICSI procedures when applied to Klinefelter patients. It is also in agreement with previous studies in the XXY-mouse model. These spermatogenic foci most probably originate from clones of spermatogonia that have randomly lost one of the X chromosomes, probably during periods of life when high spermatogonial mitotic activity occurs.

Live Offspring from Mice Lacking the Y Chromosome Long Arm Gene Complement1

The mouse Y chromosome long arm (Yq) comprises approximately 70 Mb of repetitive, male-specific DNA together with a short (0.7-Mb) pseudoautosomal region (PAR). The repetitive non-PAR region (NPYq) encodes genes whose deficiency leads to subfertility and infertility, resulting from impaired spermiogenesis. In XSxr(a)Y*(X) mice, the only Y-specific material is provided by the Y chromosome short arm-derived sex reversal factor Sxr(a), which is attached to the X chromosome PAR; these males (NPYq- males) produce sperm with severely malformed heads and are infertile. In the present study, we investigated sperm function in these mice in the context of intracytoplasmic sperm injection (ICSI). Of 261 oocytes injected, 103 reached the 2-cell stage, and 46 developed to liveborn offspring. Using Xist RT-PCR genotyping as well as gamete and somatic cell karyotyping, all six predicted genotypes were identified among ICSI-derived progeny. The sex chromosome constitution of NPYq- males does not allow production of offspring with the same genotype, but one of the expected offspring genotypes is XY*(X)Sxr(a) (NPYq-(2)), which has the same Y gene complement as NPYq-. Analysis of NPYq-(2) males revealed they had normal-sized testes with ongoing spermatogenesis. Like NPYq- males, these males were infertile, and their sperm had malformed heads that nevertheless fertilized eggs via ICSI. In vitro fertilization (IVF), however, was unsuccessful. Overall, we demonstrated that a lack of NPYq-encoded genes does not interfere with the ability of sperm to fertilize oocytes via ICSI but does prevent fertilization via IVF. Thus, NPYq-encoded gene functions are not required after the sperm have entered the oocyte. The present work also led to development of a new mouse model lacking NPYq gene complement that will facilitate future studies of Y-encoded gene function.

A new pericentromeric repeated DNA sequence in Microtus thomasi

Several karyotypic forms have been previously described in populations of the vole species Microtus thomasi from Greece. In particular, the karyomorphs Microtus thomasi ‘thomasi’ and ‘atticus’ differ in X chromosome morphology, being acrocentric and subtelocentric, respectively. Furthermore, remarkable heterochromatin content variability has been described in sex chromosomes of both karyomorphs. Genomic DNA digestion with AluI allowed us to clone an 884 bp long repeated DNA sequence (Mth-Alu900) from the karyomorph M. thomasi ‘atticus’. This repeated DNA is AT rich and seems to be organized mainly as a dimer of the 884-bp unit, which presents three simple repeats (CAAAT, CAGAT and CAGAC) that constitute 80% of the total unit length. This repeated DNA is exclusive to M. thomasi, since it is absent from the genome of other studied Arvicolinae species. The chromosomal location of Mth-Alu900 was analyzed on M. thomasi ‘thomasi’ and M. thomasi ‘atticus’ karyomorphs, with different sex chromosome constitution. It was mainly located on the pericentromeric heterochromatin of most autosomes and X chromosomes on both karyomorphs. Results are also discussed in relation to karyotypic and sex chromosome variations in M. thomasi. To our knowledge, Mth-Alu900 constitutes a new – the third discovered so far – pericentromeric repeated DNA sequence described in Microtus species.

Germ cell sex determination in mammals.

One of the major decisions that germ cells make during their development is whether to differentiate into oocytes or sperm. In mice, the germ cells’ decision to develop as male or female depends on sex-determining signalling molecules in the embryonic gonadal environment rather than the sex chromosome constitution of the germ cells themselves. In response to these sex-determining cues, germ cells in female embryos initiate oogenesis and enter meiosis, whereas germ cells in male embryos initiate spermatogenesis and inhibit meiosis until after birth. However, it is not clear whether the signalling molecules that mediate germ cell sex determination act in the developing testis or the developing ovary, or what these signalling molecules might be. Here, we review the evidence for the existence of meiosis-inducing and meiosis-preventing substances in the developing gonad, and more recent studies aimed at identifying these molecules in mice. In addition, we discuss the possibility that some of the reported effects of these factors on germ cell development may be indirect consequences of impairing sexual differentiation of gonadal somatic cells or germ cell survival. Understanding the molecular mechanisms of germ cell sex determination may provide candidate genes for susceptibility to germ cell tumours and infertility in humans.

A hypothesis explaining the exceptional sex ratio in the wood lemming (Myopus schisticolor)

The wood lemming is unique in the following respects: (1) the sex ratio is unequal, the frequency of males is 0.20–0.30; (2) two types of females occur, type MF producing progeny of both sexes, type F producing daughters only; and (3) two sex chromosome types of females exist, XX and XY. The hypothesis presented accounts for these and other known facts concerning sex ratio, reproduction biology and chromosome constitution. It is suggested that an X-linked mutant gene affects the male-determining action of the Y, thus converting some XY animals into females. These females normally produce one kind of eggs only; by a mechanism of selective non-disjunction in the foetal ovary only X-carrying eggs are formed. Thus, XY females are of type F, XX of type MF.

Centromere repositioning in the X chromosome of XO/XO mammals, Ryukyu spiny rat

Two species of Ryukyu spiny rat, Tokudaia osimensis and Tokudaia tokunoshimensis, have an XO/XO sex chromosome constitution with no cytogenetically visible Y chromosome in both sexes. The single X chromosomes of T. osimensis and T. tokunoshimensis are submetacentric and subtelocentric, respectively. It was therefore suggested that a pericentric inversion event occurred in the X chromosome of either species. To identify X chromosome rearrangements that have occurred between the two species, we mapped 22 mouse cDNA clones of the X-linked genes on the chromosomes of the two species by direct R-banding FISH. The gene orders of the X chromosomes were conserved in the two species, whereas the position of the centromere on the X chromosome was different. This result indicates that the rearrangement which occurred in either of the X chromosomes after the two species diverged from a common ancestor involved not pericentric inversion but centromere repositioning.

Sex chromosome abnormalities in natural populations of the common vole (Microtus arvalis).

Four specimens with an aberrant sex chromosome constitution were found in natural populations of the common vole (Microtus arvalis). Two females had an X0 sex chromosome constitution and single males were 2n = 47, XXY and 2n = 47, XYY, respectively. No apparent phenotypical anomalies were recorded in the sex chromosome aneuploids, but their fertility may have been impaired. The incidence of sex chromosome aneuploidy seems to be unusually high in natural populations of the common vole (1.5% of animals examined). Possible explanations for this are discussed.

Craniofacial complex specificities in five men with sex reversal syndrome

In order to clarify the role of sex chromosome constitution in craniofacial growth control, we compared craniofacial morphology of men with sex reversal syndrome (46, XX) with the morphology of normal men, Klinefelter's syndrome and normal women, using cephalometric measurements. Due to physical resemblance between men with 46, XX karyotype and men with 47, XXY karyotype, cephalometric analysis comprised parametres which had already been found to be specific for Klinefelter's syndrome, i.e. cranial base length and flexion, maxillary and mandibular base length, jaw position in relation to cranial base and sagittal jaw relationship. Linear measurements showed reduction of about 10% in maxillary base length in 46, XX men in relation to normal men. Mandibular base in men with sex reversal syndrome was also shortened for about 10% in relation to both normal men and Klinefelter's syndrome. Cranial base flexion in men with Klinefelter's syndrome and in men with sex reversal syndrome showed similarity. The basal angle was found to be more acute, for about 4 degrees , in comparison to individuals with normal karyotype. Unlike in men with Klinefelter's syndrome, mandibular and maxillary prognathism were not registered in men with sex reversal syndrome.

Nonautonomous Sex Determination Controls Sexually Dimorphic Development of the Drosophila Gonad

Sex determination in Drosophila is commonly thought to be a cell-autonomous process, where each cell decides its own sexual fate based on its sex chromosome constitution (XX versus XY). This is in contrast to sex determination in mammals, which largely acts nonautonomously through cell-cell signaling. Here we examine how sexual dimorphism is created in the Drosophila gonad by investigating the formation of the pigment cell precursors, a male-specific cell type in the embryonic gonad. Surprisingly, we find that sex determination in the pigment cell precursors, as well as the male-specific somatic gonadal precursors, is non-cell autonomous. Male-specific expression of Wnt2 within the somatic gonad triggers pigment cell precursor formation from surrounding cells. Our results indicate that nonautonomous sex determination is important for creating sexual dimorphism in the Drosophila gonad, similar to the manner in which sex-specific gonad formation is controlled in mammals.

Is the prevalence of Klinefelter syndrome increasing?

The birth prevalence of sex chromosome trisomies (SCT), that is individuals with an XYY, XXY or XXX sex chromosome constitution, is traditionally based on six surveys of unselected newborns carried out in the 1960s and early 1970s. All three SCTs had a prevalence of 1 in 1000 same sex births. We re-examined these prevalences based on additional cytogenetic studies of newborn surveys, spontaneous abortions, perinatal deaths and prenatal diagnoses. The more recent newborn surveys suggest there has been an increase in the prevalence of XXYs, but not of the other two SCTs since the original newborn series. The prevalence of XXYs has risen from 1.09 to 1.72 per 1000 male births (P=0.023). We suggest that such an increase, in the absence of an increase in the prevalence of XXX, is unlikely to be due to increased maternal age. As XXY is the only chromosome abnormality known where a substantial proportion ( approximately 50%) arise as the result of non-disjunction at the first paternal meiotic division, we speculate that some factor may be interfering with pairing and/or recombination of the sex bivalent at the paternal MI division.

Abnormal Sex Chromosome Constitution and Longitudinal Growth: Serum Levels of Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein-3, Luteinizing Hormone, and Testosterone in 109 Males with 47,XXY, 47,XYY, or Sex-Determining Region of the Y Chromosome (SRY)-Positive 46,XX Karyotypes

Growth is a highly complex process regulated by the interaction between sex steroids and the GH IGF-axis. However, other factors such as sex chromosome-related genes play independent roles. The aim of the study was to evaluate the role of abnormal chromosome constitution for longitudinal growth in relation to reproductive hormones, IGF-I, and IGF binding protein (IGFBP)-3. The study was conducted at an outpatient clinic, Copenhagen University Hospital. Participants included 86 47,XXY males, 14 46,XX-males, and nine 47,XYY. Standing and sitting height, serum levels of reproductive hormones, IGF-I, and IGFBP-3 were measured. In boys with 47,XXY and 47,XYY karyotypes, growth was accelerated already in childhood, compared with healthy boys. 46,XX-males were significantly shorter than healthy boys but matched the stature of healthy girls. In 47,XXY sitting height to height ratios were lower than expected, whereas body proportions in 46,XX-males and 47,XYY were normal. In all subjects serum levels of IGF-I and IGFBP-3 were within normal limits. The boys with 46,XX and 47,XXY karyotypes presented with low normal testosterone and elevated LH levels after puberty, whereas the sex hormone secretion of the 47,XYY boys remained normal. We found accelerated growth in early childhood in boys with 47,XXY and 47,XYY karyotypes, whereas 46,XX-males were shorter than controls. These abnormal growth patterns were not reflected in circulating levels of IGF-I and IGFBP-3. The boys with 46,XX and 47,XXY karyotypes developed hypogonadism in puberty, but androgen secretion in 47,XYY boys remained normal. The abnormal stature of these patients may be a result of abnormal gene expression due to the underlying chromosome aberration resulting in excessive expression of growth-related genes.

Evolution of multiple sex chromosomes in the spider genus Malthonica (Araneae: Agelenidae) indicates unique structure of the spider sex chromosome systems

Most spiders exhibit a multiple sex chromosome system, X(1)X(2)0, whose origin has not been satisfactorily explained. Examination of the sex chromosome systems in the spider genus Malthonica (Agelenidae) revealed considerable diversity in sex chromosome constitution within this group. Besides modes X(1)X(2)0 (M. silvestris) and X(1)X(2)X(3)0 (M. campestris), a neo-X(1)X(2)X(3)X(4)X(5)Y system in M. ferruginea was found. Ultrastructural analysis of spread pachytene spermatocytes revealed that the X(1)X(2)0 and X(1)X(2)X(3)0 systems include a pair of homomorphic sex chromosomes. Multiple X chromosomes and the pair exhibit an end-to-end pairing, being connected by attachment plaques. The X(1)X(2)X(3)X(4)X(5)Y system of M. ferruginea arose by rearrangement between the homomorphic sex chromosome pair and an autosome. Multiple X chromosomes and the sex chromosome pair do not differ from autosomes in a pattern of constitutive heterochromatin. Ultrastructural data on sex chromosome pairing in other spiders indicate that the homomorphic sex chromosome pair forms an integral part of the spider sex chromosome systems. It is suggested that this pair represents ancestral sex chromosomes of spiders, which generated multiple X chromosomes by non-disjunctions. Structural differentiation of newly formed X chromosomes has been facilitated by heterochromatinization of sex chromosome bivalents observed in prophase I of spider females.

Comparative chromosome painting map between two Ryukyu spiny rat species, Tokudaia osimensis and Tokudaia tokunoshimensis (Muridae, Rodentia)

Ryukyu spiny rats (genus Tokudaia) are indigenous species that are confined to three islands of the Nansei Shoto archipelago, Amami-Oshima, Tokunoshima and Okinawa-jima, Japan. Tokudaia tokunoshimensis from Tokunoshima Island and Tokudaia osimensis from Amami-Oshima Island are closely related taxonomically, although their karyotypes are quite different: the diploid chromosome numbers and sex chromosome constitution are 2n=45, X0/X0 for T. tokunoshimensis and 2n=25, X0/X0 for T. osimensis. We conducted comparative chromosome painting with chromosome-specific DNA probes of the laboratory mouse (Mus musculus) to molecularly examine the chromosome homology between T. tokunoshimensis and T. osimensis, and deduced a possible ancestral karyotype of Tokudaia species and the process of evolutionary chromosome rearrangements. The proposed ancestral karyotype with the diploid number of 2n=48, XX/XY was similar to the karyotype of T. tokunoshimensis, and the karyotype of T. osimensis would then have been established through at least 14 chromosomal changes, mainly centric fusion and tandem fusion, from the ancestral karyotype. The close karyological relationship between the ancestral karyotypes of Tokudaia and Apodemus also suggests that the chromosomal evolution in the Tokudaia-Apodemus lineage has been very slow and has accelerated only recently in the branch leading to T. osimensis.

Exceptional minute sex-specific region in the X0 mammal, Ryukyu spiny rat

The Ryukyu spiny rats (genus Tokudaia) inhabit only three islands in the Nansei Shoto archipelago in Japan, and have the variations of karyotype among the islands. The chromosome number of T. osimensis in Amami-Oshima Island is 2n = 25, and T. tokunoshimensis in Tokunoshima Island is 2n = 45, and the two species have X0 sex chromosome constitution with no cytogenetically visible Y chromosome in both sexes. We constructed the standard ideograms for these species at the 100 and 200 band levels. Comparing the banding patterns between these species, it was suggested that at least 10 times the number of Robertsonian fusions occurred in T. osimensis chromosomes. However, no karyotypic differences were observed between sexes in each species. To detect the sex-specific chromosomal region of these X0 species we applied the comparative genomic hybridization (CGH) method. Although the male- and female-derived gains and losses were detected in several chromosome regions, all of them were located in the heterochromatic and/or telomeric regions. This result suggested that the differences detected by CGH might be caused by the polymorphism on the copy numbers of repeated sequences in the heterochromatic and telomeric regions. Our result indicated that the sex-specific region, where the key to sex determination lies, is very minute in X0 species of Tokudaia.

The origin of an unusual sex chromosome constitution in Acomys sp. (Rodentia, Muridae) from Tanzania

This paper describes a case which presents an evident variation from the "standard" XX/XY sex chromosomal constitution in a rodent, Acomys sp. This species known to be found in three localities of East Africa has only recently been separated from A. spinosissimus, its closest relative. In our study, five specimens of Acomys sp. and eight specimens of A. spinosissimus were live-trapped in five localities. Comparisons between the two taxa assed by G-banding show a complete homology in the chromosomal shape and banding pattern for 29 pairs of chromosomes corresponding to the complete autosomal set of A. spinosissimus. However, while all the A. spinosissimus analysed have 2n = 60 and a XY-XX system, in Acomys sp. males and females constitute mosaics for sex chromosomes in the bone marrow cells. Females (2n = 59, 60) have an excess (97%) of aneuploid cells with one single giant X chromosome, and males (2n = 60, 61) show X0/XY cells occurring in somatic tissues and XY cells in the germinal lineage. In addition, an odd heterochromatic submetacentric chromosome was identified in all the cells examined in two males and a female of Acomys sp. Since this chromosome was not related to sex determination and it is not present in all the analysed specimens, it can be considered as a B chromosome. Finally, the in situ fluorescence hybridisation (FISH) with telomeric probes showed a very intense interstitial telomeric signal (ITS) at the medial part on the long heterochromatic arm of the X chromosome. This could be due to recent chromosomal rearrangement.

Influence of sex chromosome constitution on the genomic imprinting of germ cells.

Germ cells in XY male mice establish site-specific methylation on imprinted genes during spermatogenesis, whereas germ cells in XX females establish their imprints in growing oocytes. We showed previously that in vitro, sex-specific methylation patterns of pluripotent stem cell lines derived from germ cells were influenced more by the sex chromosome constitution of the cells themselves than by the gender of the embryo from which they had been derived. To see whether the same situation would prevail in vivo, we have now determined the methylation status of H19 expressed from the maternal allele, and the expression and methylation status of a paternally expressed gene Peg3, in germ cells from sex-reversed and control embryos. For these imprinted genes, we conclude that the female imprint is a response of the germ cells to undergoing oogenesis, rather than to their XX chromosome constitution. Similarly, both our XY and our sex-reversed XX male germ cells clearly showed a male rather than a female pattern of DNA methylation; here, however, the sex chromosome constitution had a significant effect, with XX male germ cells less methylated than the XY controls.

Root growth in the permanent teeth of 45,X/46,XX females

Studies on individuals with sex chromosome anomalies have provided proof of a direct differential promoting effect of the X and Y chromosome genes on tooth crown growth. 45,X/46,XX females are one subgroup of Turner patients who have both normal XX and one X sex chromosome cell lines. Their permanent tooth crown size is reduced, which is mainly due to thin enamel. 45,X females likewise show reduced crown size and enamel thickness, and their root size is reduced. By contrast, the lengths of the roots in 47,XYY males or males with an extra Y chromosome and 46,XY females or females with a male sex chromosome constitution are increased. The aim of the present study was to investigate permanent tooth root lengths in 45,X/46,XX females to obtain additional information on their dental growth. The study group consisted of 15 45,X/46,XX females, mean age 23.4 years; 10 female relatives, mean age 24.5 years; and 47 population control females, mean age 29.8 years, from the Kvantti research project. Root length measurements were made from panoramic radiographs on both sides of the jaw using a sliding digital calliper. The results showed that permanent tooth root lengths in 45,X/46,XX females were, in most cases, significantly shorter than those of the population controls or relatives. It is apparent that a reduced tooth crown size in 45,X/46,XX females is followed by reduced root growth. This begins 3 years after birth and continues to at least 14 years of age. It is suggested that the reduction in crown and root growth in 45,X/4,XX females is due to a deficiency in the amount of dental growth-promoting genes on the sex chromosomes.